Figure 8
Role of microglia in mediating bystander death of developing neurons in arsenic environment.
SA once entered into microglia (i) inhibits phosphorylation of NF-κβ thereby inhibiting expression of iNOS, TNF-α and IL-6 (ii) induces ROS which in turn enhance expression of xCT through induction of Nrf2, (iii) induces cellular GSH synthesis, which is used to efflux arsenic as GSH conjugate (As[GS]3). Induction of cellular GSH synthesis by arsenic requires intake of cystine in exchange of glutamate expelled out through xCT. Thus, microglia lower cystine from extracellular environment and at the same time accumulates glutamate. In this environment viability of developing neurons affected in two ways, in one hand low cystine level limits the supply for GSH synthesis, on the other hand higher glutamate level block the route of supply by inhibiting xCT, thereby inducing bystander death of developing neuron.
